THeragnostic utilities for neoplastic DisEases of the rectum by MRI guided radiotherapy (THUNDER 2) phase II trial: interim safety analysis
Abstract Background The THUNDER-2 phase II single institutional trial investigates the benefits of MRI-guided radiotherapy (MRIgRT) in treating locally advanced rectal cancer (LARC). This study focuses on evaluating the impact of escalating radiation therapy dose in non-responder patients using the...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2023-10-01
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| Series: | Radiation Oncology |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13014-023-02353-x |
| _version_ | 1797557455733915648 |
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| author | Giuditta Chiloiro Angela Romano Davide Cusumano Luca Boldrini Giulia Panza Lorenzo Placidi Elisa Meldolesi Matteo Nardini Guenda Meffe Gianluca Nicolini Claudio Votta Luca Indovina Maria Antonietta Gambacorta |
| author_facet | Giuditta Chiloiro Angela Romano Davide Cusumano Luca Boldrini Giulia Panza Lorenzo Placidi Elisa Meldolesi Matteo Nardini Guenda Meffe Gianluca Nicolini Claudio Votta Luca Indovina Maria Antonietta Gambacorta |
| author_sort | Giuditta Chiloiro |
| collection | DOAJ |
| description | Abstract Background The THUNDER-2 phase II single institutional trial investigates the benefits of MRI-guided radiotherapy (MRIgRT) in treating locally advanced rectal cancer (LARC). This study focuses on evaluating the impact of escalating radiation therapy dose in non-responder patients using the Early Tumour Regression Index (ERI) for predicting complete response (CR). The trial’s primary endpoint is to increase the CR rate in non-responders by 10% and assess the feasibility of the delta radiomics-based MRIgRT predictive model. This interim analysis assesses the feasibility and safety of the proposed MRIgRT dose escalation strategy in terms of acute toxicity (gastrointestinal, genitourinary and haematological) and treatment adherence. Methods Stage cT2-3, N0-2, or cT4 patients with anal sphincter involvement, N0-2a, M0, but without high-risk features were enrolled. MRIgRT treatment consisted of a standard dose of 55 Gy to the Gross Tumor Volume (GTV) and mesorectum, and 45 Gy to the mesorectum and drainage nodes in 25 fractions with concomitant chemotherapy. 0.35 T MRI was used for simulation imaging and daily alignment. ERI was calculated at the 10th fraction. Non-responders with an ERI above 13.1 received intensified dose escalation from the 11th fraction, resulting in a total dose of 60.1 Gy. Acute toxicity was assessed using the CTCAE v.5 scale. Results From March 2021 to November 2022, 33 out of the total number of 63 patients to be enrolled (52.4%) were included, with one withdrawal unrelated to treatment. Sixteen patients (50%) underwent dose escalation. Treatment was well tolerated, with only one patient (3.1%) in the standard treatment group experiencing acute Grade 3 diarrhea, proctitis, and cystitis. No significant differences in toxicity were observed between the two groups (p = 0.5463). Conclusions MRIgRT treatment with dose escalation up to 60.1 Gy is well tolerated in LARC patients predicted as non-responders by ERI, confirming the feasibility and safety of this approach. The THUNDER-2 trial’s primary and secondary endpoints will be fully analyzed when all planned patients will be enrolled. |
| first_indexed | 2024-03-10T17:17:18Z |
| format | Article |
| id | doaj.art-822c91efc4af4405a3f539bee27f52f7 |
| institution | Directory Open Access Journal |
| issn | 1748-717X |
| language | English |
| last_indexed | 2024-03-10T17:17:18Z |
| publishDate | 2023-10-01 |
| publisher | BMC |
| record_format | Article |
| series | Radiation Oncology |
| spelling | doaj.art-822c91efc4af4405a3f539bee27f52f72023-11-20T10:26:40ZengBMCRadiation Oncology1748-717X2023-10-011811810.1186/s13014-023-02353-xTHeragnostic utilities for neoplastic DisEases of the rectum by MRI guided radiotherapy (THUNDER 2) phase II trial: interim safety analysisGiuditta Chiloiro0Angela Romano1Davide Cusumano2Luca Boldrini3Giulia Panza4Lorenzo Placidi5Elisa Meldolesi6Matteo Nardini7Guenda Meffe8Gianluca Nicolini9Claudio Votta10Luca Indovina11Maria Antonietta Gambacorta12Fondazione Policlinico Universitario “Agostino Gemelli” IRCCSFondazione Policlinico Universitario “Agostino Gemelli” IRCCSMater Olbia HospitalFondazione Policlinico Universitario “Agostino Gemelli” IRCCSFondazione Policlinico Universitario “Agostino Gemelli” IRCCSFondazione Policlinico Universitario “Agostino Gemelli” IRCCSFondazione Policlinico Universitario “Agostino Gemelli” IRCCSFondazione Policlinico Universitario “Agostino Gemelli” IRCCSFondazione Policlinico Universitario “Agostino Gemelli” IRCCSFondazione Policlinico Universitario “Agostino Gemelli” IRCCSFondazione Policlinico Universitario “Agostino Gemelli” IRCCSFondazione Policlinico Universitario “Agostino Gemelli” IRCCSFondazione Policlinico Universitario “Agostino Gemelli” IRCCSAbstract Background The THUNDER-2 phase II single institutional trial investigates the benefits of MRI-guided radiotherapy (MRIgRT) in treating locally advanced rectal cancer (LARC). This study focuses on evaluating the impact of escalating radiation therapy dose in non-responder patients using the Early Tumour Regression Index (ERI) for predicting complete response (CR). The trial’s primary endpoint is to increase the CR rate in non-responders by 10% and assess the feasibility of the delta radiomics-based MRIgRT predictive model. This interim analysis assesses the feasibility and safety of the proposed MRIgRT dose escalation strategy in terms of acute toxicity (gastrointestinal, genitourinary and haematological) and treatment adherence. Methods Stage cT2-3, N0-2, or cT4 patients with anal sphincter involvement, N0-2a, M0, but without high-risk features were enrolled. MRIgRT treatment consisted of a standard dose of 55 Gy to the Gross Tumor Volume (GTV) and mesorectum, and 45 Gy to the mesorectum and drainage nodes in 25 fractions with concomitant chemotherapy. 0.35 T MRI was used for simulation imaging and daily alignment. ERI was calculated at the 10th fraction. Non-responders with an ERI above 13.1 received intensified dose escalation from the 11th fraction, resulting in a total dose of 60.1 Gy. Acute toxicity was assessed using the CTCAE v.5 scale. Results From March 2021 to November 2022, 33 out of the total number of 63 patients to be enrolled (52.4%) were included, with one withdrawal unrelated to treatment. Sixteen patients (50%) underwent dose escalation. Treatment was well tolerated, with only one patient (3.1%) in the standard treatment group experiencing acute Grade 3 diarrhea, proctitis, and cystitis. No significant differences in toxicity were observed between the two groups (p = 0.5463). Conclusions MRIgRT treatment with dose escalation up to 60.1 Gy is well tolerated in LARC patients predicted as non-responders by ERI, confirming the feasibility and safety of this approach. The THUNDER-2 trial’s primary and secondary endpoints will be fully analyzed when all planned patients will be enrolled.https://doi.org/10.1186/s13014-023-02353-xMagnetic resonance guided Radiation TherapyRectal cancerChemoradiotherapyEarly Regression IndexRadiomicsDose escalation |
| spellingShingle | Giuditta Chiloiro Angela Romano Davide Cusumano Luca Boldrini Giulia Panza Lorenzo Placidi Elisa Meldolesi Matteo Nardini Guenda Meffe Gianluca Nicolini Claudio Votta Luca Indovina Maria Antonietta Gambacorta THeragnostic utilities for neoplastic DisEases of the rectum by MRI guided radiotherapy (THUNDER 2) phase II trial: interim safety analysis Radiation Oncology Magnetic resonance guided Radiation Therapy Rectal cancer Chemoradiotherapy Early Regression Index Radiomics Dose escalation |
| title | THeragnostic utilities for neoplastic DisEases of the rectum by MRI guided radiotherapy (THUNDER 2) phase II trial: interim safety analysis |
| title_full | THeragnostic utilities for neoplastic DisEases of the rectum by MRI guided radiotherapy (THUNDER 2) phase II trial: interim safety analysis |
| title_fullStr | THeragnostic utilities for neoplastic DisEases of the rectum by MRI guided radiotherapy (THUNDER 2) phase II trial: interim safety analysis |
| title_full_unstemmed | THeragnostic utilities for neoplastic DisEases of the rectum by MRI guided radiotherapy (THUNDER 2) phase II trial: interim safety analysis |
| title_short | THeragnostic utilities for neoplastic DisEases of the rectum by MRI guided radiotherapy (THUNDER 2) phase II trial: interim safety analysis |
| title_sort | theragnostic utilities for neoplastic diseases of the rectum by mri guided radiotherapy thunder 2 phase ii trial interim safety analysis |
| topic | Magnetic resonance guided Radiation Therapy Rectal cancer Chemoradiotherapy Early Regression Index Radiomics Dose escalation |
| url | https://doi.org/10.1186/s13014-023-02353-x |
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